Aged Epidermis Research Articles

Biochemical parameters of epidermal aging in the hairless mouse and the relationship to UV-carcinogenesis

Epidemiological studies suggest that the incidence of cancer increases with age in both human and animal populations and that declining physiologic condition associated with aging might be responsible. Experimentally, the reverse has been most often observed, that is, older animals appear less susceptible to the induction of UV-carcinogenesis. Thus, we examined several biochemical parameters of epidermal macromolecular synthesis in hairless mice in an effort to gain insight, into the role these processes play in physiological aging and their relationship to carcinogenesis. SKh-Hr-1 hairless mice were randomized into two groups (UV-irradiated and non-irradiated controls) and were two months of age at the start of irradiation and biochemical analyses. The UV group received 0.028 sunburn units (SBUs) daily (5 days wk −1) for 16 months from 40 watt BZS-WLG lamps. Stratum corneum turnover rates (SCR), cell label index (CLI), protein, DNA and RNA synthesis, and ornithine decarboxylase (ODC) induction were determined at monthly intervals over a period of two years. There were no age-related tendencies observed in SCR. CLI increased with age. Chronic, low-dose UV had no effect upon either of these parameters. Epidermal capacity for DNA and protein synthesis increased with age from 2 months to 12–15 months at which time both parameters peaked and then began to decline. UV significantly reduced ( P<0.04) the magnitude of DNA synthetic capacity at peak periods of synthesis but had no effect upon protein synthesis. RNA synthetic rates declined with age, reaching their lowest levels at 24 months. Further, a significant reduction ( P<0.001) in ODC inducibility occurred with advancing age. Comparison of these data with UV-carcinogenesis studies indicates that macromolecular synthetic rates, i.e., DNA and protein, are lowest at times when mice are most susceptible to UV-induced carcinogenesis. Induced ODC activity, believed to be a marker of tumor promotion, was lowest at ages when mice were most refractory to induction of UV-carcinogenesis. Whereas these data provide some insight into the physiologic status of aging epidermis in the hairless mouse, the relationship to UV-carcinogenesis remains speculative.

Aged versus young skin before and after transplantation onto nude mice

The behaviour of aged skin transplanted onto nude mice was investigated to determine whether the skin maintains its histological features. Split-thickness skin grafts obtained from the unexposed skin on the thighs of healthy aged and young volunteers were grafted onto nude mice. A significant difference between the mean thickness of young versus aged epidermis was noted before transplantation (P less than 0.001). The epidermis of aged and young skin showed an increase in thickness following engraftment with a mean increase in epidermal thickness of 18.8% in the young (P less than 0.01) and 142.5% in aged skin (P less than 0.001). The number of blood vessels in the aged skin was significantly lower than in the young skin, but a remarkable increase was found post-transplantation. These findings indicate that part of the typical histological changes of unexposed aged skin are reversible.

Structural and functional changes of normal aging skin

Solar-induced cutaneous changes are more prevalent and profound in older persons and, thus, are often inappropriately attributed to the aging process, per se. Structural and functional alterations caused by intrinsic aging and independent of environmental insults are now recognized in the skin of elderly individuals. Structurally the aged epidermis likely becomes thinner, the corneocytes become less adherent to one another, and there is flattening of the dermoepidermal interface. The number of melanocytes and Langerhans cells is decreased. The dermis becomes atrophic and it is relatively acellular and avascular. Dermal collagen, elastin, and glycosaminoglycans are altered. The subcutaneous tissue is diminished in some areas, especially the face, shins, hands, and feet, while in others, particularly the abdomen in men and the thighs in women, it is increased. The number of eccrine glands is reduced and both the eccrine and apocrine glands undergo attenuation. Sebaceous glands tend to increase in size but paradoxically their secretory output is lessened. The nail plate is generally thinned, the surface ridged and lusterless, and the lunula decreased in size. There is a progressive reduction in the density of hair follicles per unit area on the face and scalp, independent of male-pattern alopecia. The hair shaft diameter is generally reduced but in some areas, especially the ears, nose, and eyebrows of men and the upper lip and chin in women, it is increased as vellus hairs convert to cosmetically compromising terminal hairs. Functional alterations noted in the skin of elderly persons include a decreased growth rate of the epidermis, hair, and nails, delayed wound healing, reduced dermal clearance of fluids and foreign materials, and compromised vascular responsiveness. Eccrine and apocrine secretions are diminished. The cutaneous immune and inflammatory responses are impaired, particularly cell-mediated immunity. Clinical correlates of these intrinsic aging changes of the skin include alopecia, pallor, xerosis, an increased number of benign and malignant epidermal neoplasms, increased susceptibility to blister formation, predisposition to injury of the dermis and underlying tissues, delayed onset and resolution of blisters and wheals, persistent contact dermatitis, impaired tanning response to ultraviolet light, increased risk for wound infections, prolongation of therapy necessary for onychomycosis, and thermoregulatory disturbances.